[Licensing Story_CJ HealthCare] CJ-12420?a stride by CJ HealthCare towards the development of a new global drug

12.29.2016

CJ-12420—a stride by CJ HealthCare towards the development of a new global drug

Ji-hye Park, CJ HealthCare

CJ-12420 belongs to a new class of acid secretion inhibitors with a novel mechanism of action. It is a lead compound of CJ Healthcare’s product pipelines of new drugs and biologics. CJ-12420 was selected as one of the global promising drug candidates by the Korea Development Drug Fund (KDDF) in 2014. Since then, financial support has continuously been made for non-clinical and clinical studies to promote the global development of CJ-12420.

Acid-related digestive disorders involve various digestive disorders associated with gastric acid. Such disorders include gastric ulcer, duodenal ulcer, erosive gastroesophageal reflux disease (GERD), and non-erosive GERD. These can be cured – or, at least, the symptoms can be alleviated significantly – by inhibiting gastric acid secretion. Acid-related diseases have recently been on the increase. This increase (which is gradual) is due to an aging population, obesity, and heavy consumption of alcohol. Acid-related diseases are likely to affect approximately 250 million people by 2020 in seven advanced countries. In particular, GERD is a common condition that develops when stomach reflux and regurgitation of the stomach’s contents causes troublesome symptoms and/or complications. Typical symptoms of GERD include heartburn and acid reflux. However, the disease is chronic with a high risk of relapse, thus causing prolonged pain.

In China, the prevalence of GERD has been increasing from 2.0% in 1994 to 8.4% in 2010. Moreover, with the rapid growth of the aging population, its GERD market size is expected to expand explosively in 2020. Furthermore, those suffering from GERD in Taiwan and Singapore (where many Chinese people are residing) are 12.4% and 10.5%, respectively, showing a relatively high prevalence of the disease (along with the aforementioned increase in the prevalence of GERD itself). In Korea, the number of patients suffering from GERD has risen annually by an average growth of more than 13% in the past five years. People in their 50s have been the ones most frequently to be diagnosed with GERD. They comprise 24.1% of the total sufferers, followed by those in their 40s, who comprise 20.5% of those suffering from the disease. Together, those in their 40s-50s accounted for 44.6% of the total number of people with the disorder. Under such circumstances, given the ever-growing aging trend, the prevalence of GERD is likely to spiral upwards. This may spur the market demand for acid suppressants.

Acid suppressants have been the biggest-selling drugs worldwide since the release of H2 receptor antagonists in the 1970s and the introduction of proton pump inhibitors (PPIs) in the late 1980s. Currently, PPIs are the main modalities in the treatment of acid-related diseases. Published reports, however, suggest the shortcomings of PPIs in that the onset of PPI action is generally slow due to the irreversible nature of its acid inhibition, its acid antisecretory effect being low after food intake, and night-time gastric acid being inadequately controlled with PPIs. Moreover, the metabolism of PPIs by polymorphic cytochrome CYP450 2C19, a drug-metabolizing enzyme, could result in varying plasma concentrations and varying acid-inhibitory effects among individual patients. Thus, there is need for the development of CJ-12420 with a novel mechanism of action to overcome the drawbacks of conventional drugs.

CJ Healthcare completed the Phase 2 clinical trial of CJ-12420 in patients with erosive GERD being treated in major university hospitals in Korea. Currently, CJ-12420 is under Phase 3 clinical study prior to the scheduled release of the product for home consumers in 2018. The clinical findings suggest that CJ-12420 can provide a strong and sustained acid-secretion-inhibitory effect with more rapid onset of action and more long-lasting effects than offered by the existing PPIs.

With the comparatively higher efficacy and market potentiality of CJ-12420, which has already been recognized as a promising acid secretion antagonist, CJ HealthCare signed an out-licensing agreement on September 2015 with Shandong Luoxin Pharmaceutical Group, one of the leading digestive firms in China. This agreement grants the Chinese firm the rights to develop, manufacture, and sell “CJ-12420” as a medication to treat GERD. This is an achievement made only five years since CJ HealthCare started to initiate preclinical studies for CJ-12420 in 2010. Furthermore, in consideration of the acid-suppressant market being valued at 3 trillion won, and in consideration of the rapidly-expanding antiulcer market size, it can be safely said that CJ Healthcare’s technology transfer of CJ-12420 is a meaningful event. The agreement generated a total revenue of approximately 100 billion won for CJ HealthCare—the largest business deal made between local and Chinese companies.

The driving forces of an such achievement are mainly attributable to the following factors: clear and definitive development objectives that had been firmly established at an earlier stage; an in-depth understanding of digestive diseases; development capability; and a limitless aspiration for target achievement.

Our initial preclinical development strategy for CJ-12420 was to focus on the rapidly-expanding Chinese and domestic market for anti-acid-secretory drugs. CJ-12420’s target patients were people with acid-related disease such as GERD (there being a high proportion of CAGR in China), gastric ulcer/gastritis (there being a gradual increase in the prevalence of this), and Helicobacter pylori infection (which has proven unresponsive to triple therapy treatments following its re-emergence after eradication). We designed preclinical and clinical studies with an aim to differentiate the efficacy and properties of CJ-12420 from those of conventional products; and we carried out all studies based upon our initial program. From the data yielded by the target-oriented strategy, we could demonstrate the differentiated pharmacology and excellent efficacy/safety profiles of CJ-12420 over the existing medicines. CJ Healthcare’s consistent development strategy made it possible to gain the firm trust and great confidence of our Chinese partner in the process of negotiating the technical transfer, which in turn has helped Shandong Luoxin establish its development and marketing strategies in China.

The process of developing a new drug can be compared to the collaboration of expert artists in designing and creating a world-class masterpiece painting. Picturing the end product, related departments expert at their craft (e.g., manufacturing plant, business development, license & registration, and marketing) work together in full collaboration with a laboratory institute. In the case of CJ-12420, people in all related departments made their utmost efforts to complete this wonderful picture by providing all possible cooperation at each phase of development and at critical moments. Thanks to everyone’s affection for and passion towards this one project in an organized manner, we could (to a great extent) attain our objectives. For the same reasons, we are also convinced that together, an even larger picture may be painted in the near future.

Based on the outstanding pharmacological results of the pre-clinical and Phase I/II clinical studies, we will continue to prioritize patient safety first while secondarily maximizing the licensing value of CJ-12420 by executing preclinical and clinical studies for differentiated efficacy and long-term safety. Cross-marketing efforts will also be made so that CJ-12420 may be marketed in more 'pharmerging' markets. CJ HealthCare is also striving to become one of the global pharmaceutical companies that has the capacity to develop CJ-12420 as a global blockbuster drug.